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Background: Associations between high physical activity (PA) levels and incident atrial fibrillation (AF) is found in some earlier studies. We aim to study the association between levels of PA and AF in two cohorts. Methods: We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM) study, initiated in 1970, included men aged 50 years, with 2202 included in the study. Examinations were reiterated three times, with follow-up after in median 33 years, with 3.8–6.0% on the highest PA level. We also used data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; with women 50%); mean age 70 years, baseline 2001–2004, median follow-up 15 years, with 961 included in the study, with 4.8% on the highest PA level. Cox regression analysis with hazard ratios (HRs) was used to study association between PA levels and incident AF, adjusted for CV risk factors: systolic blood pressure, LDL- and HDL-cholesterol, BMI, diabetes, and smoking. Results: Totally, in ULSAM 504 men during 59,958 person-years at risk, and in PIVUS 204 individuals during a follow-up of 11,293 person-years experienced an AF. Neither in ULSAM, PIVUS, nor in the meta-analysis of both cohorts, individuals with the highest PA level showed an increased AF risk, compared to individuals with lowest level of PA. Conclusions: The benefits of PA in community dwelling individuals for its benefits to mental, metabolic, and cardiovascular health should guide public recommendations, rather than a possible risk of AF. Lay Summary: We studied the risk of incident atrial fibrillation at various levels of physical activity in two cohorts and found no statistically significant increased risk after adjusting for cardiovascular risk factors (systolic blood pressure, LDL- and HDL-cholesterol, BMI, diabetes, and smoking).

The detrimental effects of increased length of stay at the emergency department (ED-LOS) for patient outcome have been sparsely studied in the Swedish setting. Our aim was to further explore the association between ED-LOS and short-term mortality in patients admitted to the EDs of two large University hospitals in Sweden. All adult patients (> 18 years) visiting the ED at the Karolinska University Hospital, Sweden, from 1/1/2010 to 1/1/2015 (n = 639,385) were retrospectively included. Logistic regression analysis was used to determine association between ED-LOS and 7- and 30-day mortality rates. All patients were triaged according to the RETTS-A into different levels of medical urgency and subsequently separated into five quintiles of ED-LOS. Mortality rate was highest in highest triage priority level (7-day mortality 5.24%, and 30-day mortality 9.44%), and decreased by lower triage priority group. For patients with triage priority levels 2–4, prolonged ED-LOS was associated with increased mortality, especially for lowest priority level, OR for priority level 4 and highest quintile of ED-LOS 30-day mortality 1.49 (CI 95% 1.20–1.85). For patients with highest triage priority level the opposite was at hand, with decreasing mortality risk with increasing quintile of ED-LOS for 7-day mortality, and lower mortality for the two highest quintile of ED-LOS for 30-day mortality. In patients not admitted to in-hospital care higher ED-LOS was associated with higher mortality. Our data suggest that increased ED-LOS could be associated with slightly increased short-term mortality in patients with lower clinical urgency and dismissed from the ED.

Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful. Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes. Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate <60 mg/mL/1.73 m 2 and/or urinary albumin-creatinine ratio ≥3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline. Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors. Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.

Aims/hypothesisMultiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes.MethodsWe combined data from six prospective epidemiological studies of 30–77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample.ResultsOf 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (±SD) of 6.4 ± 2.3 years. We replicated associations (<5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit α (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample.Conclusions/interpretationWe identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.

Aims/hypothesis Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease. Methods The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used. Results Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32–1.93, p < 0.001 and OR 1.54, 95 % CI 1.21–1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29–2.174, p < 0.001 and HR 1.47, 95 % CI 1.13–1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality. Conclusions/Interpretations Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

Child sexual abuse (CSA) is a crime against human rights with severe health consequences, and suicidal actions, stress, eating disorders, and borderline disorder are common among survivors of CSA. The objective of this study was to analyze how health care consumption patterns developed among adolescent girls in the Stockholm Region, Sweden, 1 and 2 years after the first registration of CSA experience appeared in their medical record, as compared to age-matched controls without such registration. In this cohort study, number of healthcare visits, comorbidities, and prescribed drugs were collected through the Stockholm Region administrative database (VAL), for girls age 12–17 with registration of CSA experience in their medical record (n = 519) and age-matched controls (n = 4920) between 2011 and 2018. Healthcare consumption patterns remained higher among the girls with a registered CSA experience compared to the controls, both 1 and 2 years after the first CSA experience registration. Highest odds ratios (ORs) were found for suicide attempts [OR 26.38 (12.65–55.02) and 6.93 (3.48–13.49)]; stress disorders [25.97 (17.42–38.69) and 15.63 (9.82–24.88)]; psychosis [OR 19.39 (1.75–214.13) and 9.70 (1.36–68.95)], and alcohol abuse [OR 10.32 (6.48–16.44) and 6.09 (1.98–18.67)], 1 and 2 years, respectively, after the first CSA experience registration. The drug prescriptions were also significantly higher among the girls with a CSA experience registration than for the controls. The results highlight the need to systematically evaluate and develop assessment, treatment planning, and interventions offered to adolescent girls after their first CSA experience registration.

Victims of sexual abuse have more co-morbidities than other persons in the same age and the most affected group are adolescent girls. Little is known about how this is reflected in health care consumption patterns prior to the registered diagnosis. The aim of this investigation was to study health care consumption patterns among girls, 12–17 years old, 1 and 2 years prior to their diagnoses of sexual abuse. Through the Stockholm Region administrative database (VAL), data of co-morbidities, number of health care visits, and prescribed drugs were collected for cases (girls age 12–17 with diagnoses of sexual abuse, n = 519) and controls matched for age and socio-economic status (n = 4920) between 2011–2018. Health care consumption and co-morbidities were significantly higher for the cases compared to controls, with a rise 1 year before the diagnoses: the total number of health care visits (including no shows) 1 year prior to the first recording of the diagnosis was 20.4 (18.1–22.7) for the cases and 6.2 (5.8–6.6) for the controls. The most frequent visits 1 year prior to the diagnosis were to outdoor clinics, with a mean value of 19.1 (16.9–21.3) visits for the cases and 5.7 (5.3–6.1) for the controls, followed by psychiatric clinics with a mean value of 12.7 (10.6–14.8) visits for the cases and 2.0 (1.7–2.3) visits for the controls. The least visited health care clinic 1 year prior to the diagnosis was the emergency ward with a mean value of 1.3 (1.1–1.5) visits for the cases and 0.5 (0.4–0.5) visits for the controls. The most common psychiatric co-morbidities registered among the cases during the first year before the diagnosis of sexual abuse were stress, suicide attempt, and psychosis. Neuroleptics, sleeping pills, antidepressants, and tranquilizers were more frequently dispensed in cases than in controls. Similar patterns were found 2 years prior to the diagnosis. We encourage clinicians to actively ask for exposure of sexual abuse in girls with high health care consumption, making early detection and treatment of sexual abuse available as soon as possible.

BackgroundPrior research based on self-reports has proven sexual abuse to be a risk factor for pain and psychiatric disorders. However, less is known about how this is reflected within the healthcare system. The aim of this study was to study the 2-year prevalence of diagnosis of sexual abuse and concomitant conditions.MethodsUsing data from VAL, the study population included all living persons in Stockholm County, Sweden, between 1 January 2008 and 31 December 2014 (N=2 549 496). Diagnoses of sexual abuse were identified during 2013–2014, with information on the concomitant conditions somatic pain, depression, anxiety, psychotic disorders and bipolar disorders, stress disorders and alcohol and substance abuse. All diagnoses were prospectively registered. Age and neighbourhood socioeconomic status-adjusted ORs with 95% CIs for individuals with a diagnosis of sexual abuse, using individuals without sexual abuse as referents, were calculated.ResultsGirls at the ages 13–17 years had the highest 2-year prevalence (0.69%) of sexual abuse followed by girls 5–12 years (0.11%), and girls 0–4 years (0.04%). For women 45 years and older the 2-year prevalence rates were substantially lower (0.008–0.004%). The highest 2-year prevalence of sexual abuse in men was seen in boys 5–12 (0.03%) years. The total 2-year prevalence of diagnoses of sexual abuse among the population in the material was 0.04%. The highest ORs of comorbidities for girls (ages 0–17 years) with sexual abuse versus those without sexual abuse were: Stress disorder; 15.7 (13.1 to 18.9), drug abuse; 10.0 (7.7 to 13.0), and alcohol abuse; 9.7(7.8 to 12.0). For boys (ages 0–17 years), the highest ORs of comorbidities were: Stress disorder 12.4 (6.0 to 25.7), anxiety disorders; 5.5 (2.6 to 11.5), and alcohol abuse; 3.9 (1.4 to 11.3). The highest ORs of comorbidities for women (18–) with sexual abuse versus those without sexual abuse were: alcohol abuse; 19.3 (12.6 to 29.6), drug abuse; 16.7 (10.7 to 26.1) and psychotic disorders; 15.3 (8.0 to 29.4). For men (18–) the highest ORs of comorbidities were: alcohol abuse; 25.8 (15.2 to 43.9), anxiety disorders; 14.3 (8.5 to 24.2) stress disorder; 12.9 (7.5 to 22.1) and drug abuse; 12.9 (6.9 to 24.1).ConclusionsDiagnoses of drug and alcohol abuse, psychotic, bipolar, stress anxiety disorders, depression and somatic pain are more common among individuals with a diagnosis of sexual abuse than among individuals without a diagnosis of sexual abuse.